Hu Jing, Zhang Fuyi, Qin Xiaoshan, Nong Xinlei, Shi Xiaoyan, Zhou Xihan, Qin Yueqiu
Digestive Endoscopy Center, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise 533000, China.
Department of Nephrology, Affiliated Hospital of Youjiang Medical University for Nationalities, Guangxi Zhuang Autonomous Region, Baise533000, China.
Chem Res Toxicol. 2025 Jan 20;38(1):46-57. doi: 10.1021/acs.chemrestox.4c00208. Epub 2024 Dec 27.
Ferroptosis is regarded as a promising cancer therapeutic target. As a major bioactive compound from traditional Chinese medicine (TCM) herb Aiton, oxymatrine (OMT) can depress inflammatory factors, reduce iron deposition, and suppress the hub gene or protein expression involved in ferroptosis and inflammation. Additionally, OMT can control collagen deposition in the liver and has a therapeutic effect on liver cancer. This research investigated the action mechanism of the mechanism of the effect of OMT on the process of liver cancer. OMT triggered cell death and restrained cell proliferation in liver cancer cells, along with downregulated levels of Yin Yang 1 (YY1) and glutathione peroxidase 4 (GPX4) and elevated expression of silent information regulator 1 (SIRT1). Moreover, ferroptosis is the main method leading to OMT-induced liver cancer cell death. OMT-induced ferroptosis was reversed after GPX4 and YY1 overexpression or inhibition of SIRT1. Furthermore, the OMT restrained tumor growth through the SIRT1/YY1/GPX4 axis in liver cancer transplantation models. These results indicated that OMT inhibited cell viability and induced ferroptosis of liver cancer cells, involving the regulatory mechanism of the SIRT1/YY1/GPX4 axis.
铁死亡被认为是一个有前景的癌症治疗靶点。氧化苦参碱（OMT）作为传统中药艾氏植物中的一种主要生物活性化合物，可抑制炎症因子、减少铁沉积，并抑制参与铁死亡和炎症的关键基因或蛋白表达。此外，OMT可控制肝脏中的胶原蛋白沉积，对肝癌具有治疗作用。本研究探讨了OMT对肝癌进程影响的作用机制。OMT可引发肝癌细胞死亡并抑制其增殖，同时下调阴阳1（YY1）和谷胱甘肽过氧化物酶4（GPX4）水平，并上调沉默信息调节因子1（SIRT1）的表达。此外，铁死亡是导致OMT诱导肝癌细胞死亡的主要方式。在GPX4和YY1过表达或抑制SIRT1后，OMT诱导的铁死亡被逆转。此外，在肝癌移植模型中，OMT通过SIRT1/YY1/GPX4轴抑制肿瘤生长。这些结果表明，OMT抑制肝癌细胞活力并诱导其铁死亡，涉及SIRT1/YY1/GPX4轴的调控机制。
